Elimination Mechanisms in the Aminolysis of Sulfamate Esters of the Type NH2SO2OC6H4X – Models of Enzyme Inhibitors

Spillane, William J.; O'Byrne, Andrew B.; McCaw, Cheryl J. A.

doi:10.1002/ejoc.200800366

Cited by 16 publications

(11 citation statements)

References 19 publications

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“…This value is quite close to the value calculated using the linear free energy relationship data reported in the literature. In alkaline conditions, sulfamate esters react through the path shown in Scheme …”

Section: Resultssupporting

confidence: 54%

“…The O―S bond cleavage occurs through an E1cB mechanism and a sulfur trioxide‐like transition state . For substituted aryl sulfamate esters, this reaction has a β lg value of −1.20 in water at 25 °C, similar to the observed reaction of substituted aryl N ‐phenylmethylsulfamates with tert ‐butylamine in CH 3 CN ( β lg = −1.25 at 25 °C) .…”

Section: Resultsmentioning

confidence: 59%

“…[50,51] The O-S bond cleavage occurs through an E1cB mechanism and a sulfur trioxide-like transition state. [50][51][52][53] For substituted aryl sulfamate esters, this reaction has a β lg value of À1.20 in water at 25°C, [52] similar to the observed reaction of substituted aryl N-phenylmethylsulfamates with tert-butylamine in CH 3 CN (β lg = À1.25 at 25°C). [54] A HN¼SO 2 species is proposed to be the intermediate before the nucleophilic attack that gives the final products.…”

Section: Correlation Between Structural Parameters and Effective Charmentioning

confidence: 99%

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Linear correlation between effective charge and bond length sensitivity to electronic effects in phosphoryl, sulfonyl, and sulfuryl compounds

Brandão

2013

J of Physical Organic Chem

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This work presents a linear correlation between bond length sensitivity (Δr/ΔpKlg) and effective charge by comparing a series of the following ROX compounds bearing phosphoryl (XP) and sulfonyl and sulfuryl (XS) moieties: phosphate monoester dianions and monoanions, phosphate diesters, phosphate and phosphorothioate triesters, 4‐Me, 3‐NO2 and 2‐ or 4‐NO2 substituted aryl benzene sulfonates, sulfate monoesters, and a previously determined series of sulfamate and mesylate esters. In every series for ROX compounds, the shortest C―O bond corresponds to the longest O―X bond, showing a linear correlation with the pKlg of the ROH parent compound. The chemical reasons for the extent of bond elongation are discussed, and a linear correlation is found between O―X bond length sensitivity and effective charge. These data show that bond length elongation depends on its strength regarding the equilibrium related to the full bond cleavage. Effective charges for phosphorothioate triesters and sulfonates are estimated, and the effective charge for aryl sulfamate esters is determined on the basis of the available linear free energy relationship data. It is expected that the observations of this paper will illuminate the effect of the electronic demand on the O―X bond lengths during phosphoryl, sulfonyl, and sulfuryl group transfer. Copyright © 2013 John Wiley & Sons, Ltd.

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Section: Resultssupporting

confidence: 54%

Section: Resultsmentioning

confidence: 59%

Section: Correlation Between Structural Parameters and Effective Charmentioning

confidence: 99%

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Linear correlation between effective charge and bond length sensitivity to electronic effects in phosphoryl, sulfonyl, and sulfuryl compounds

Brandão

2013

J of Physical Organic Chem

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“…The syntheses of compounds 1a, 1f, 1g, 1h, 1i and 1j has been described previously 7 as have the syntheses of 1b and 1c. 18 1d and 1e were synthesised by the same methods.…”

Section: Substrates and Reagentsmentioning

confidence: 99%

Mechanisms of hydrolysis of phenyl- and benzyl 4-nitrophenyl-sulfamate esters

et al. 2011

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The kinetics of hydrolysis at medium acid strength (pH interval 2-5) of a series of phenylsulfamate esters 1 have been studied and they have been found to react by an associative S(N)2(S) mechanism with water acting as a nucleophile attacking at sulfur, cleaving the S-O bond with simultaneous formation of a new S-O bond to the oxygen of a water molecule leading to sulfamic acid and phenol as products. In neutral to moderate alkaline solution (pH ≥ ~ 6-9) a dissociative (E1cB) route is followed that involves i) ionization of the amino group followed by ii) unimolecular expulsion of the leaving group from the ionized ester to give N-sulfonylamine [HN=SO(2)] as an intermediate. In more alkaline solution further ionization of the conjugate base of the ester occurs to give a dianionic species which expels the aryloxide leaving group to yield the novel N-sulfonylamine anion [(-)N=SO(2)]; in a final step, rapid attack of hydroxide ion or a water molecule on it leads again to sulfamic acid. A series of substituted benzyl 4-nitrophenylsulfamate esters 4 were hydrolysed in the pH range 6.4-14, giving rise to a Hammett relationship whose reaction constant is shown to be consistent with the E1cB mechanism.

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“…The instability of primary phenol O-sulfamates under basic conditions is due to an E1Cb mechanism in which deprotonation of one of the sulfamate NH 2 protons precedes elimination of the phenol. 5 Reported protecting groups for sulfamates include N-alkyloxycarbonyl (alkyl = t-butyl-, 6 benzyl- 7 or methyl- 8 ) and the N-tbutyl group. 9 However, these groups all retain one proton on the sulfamate nitrogen and the sulfamate is still vulnerable to E1Cb degradation.…”

Section: Resultsmentioning

confidence: 99%

Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups

et al. 2012

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Sulfamates are important functional groups in certain areas of current medicinal chemistry and drug development. Alcohols and phenols are generally converted into the corresponding primary sulfamates (ROSO(2)NH(2) and ArOSO(2)NH(2), respectively) by reaction with sulfamoyl chloride (H(2)NSO(2)Cl). The lability of the O-sulfamate group, especially to basic conditions, usually restricts this method to a later stage of a synthesis. To enable a more flexible approach to the synthesis of phenolic O-sulfamates, a protecting group strategy for sulfamates has been developed. Both sulfamate NH protons were replaced with either 4-methoxybenzyl or 2,4-dimethoxybenzyl. These N-protected sulfamates were stable to oxidising and reducing agents, as well as bases and nucleophiles, thus rendering such masked sulfamates suitable for multi-step synthesis. The protected sulfamates were synthesised by microwave heating of 1,1'-sulfonylbis(2-methyl-1H-imidazole) with a substituted phenol to give an aryl 2-methyl-1H-imidazole-1-sulfonate. This imidazole-sulfonate was N-methylated by reaction with trimethyloxonium tetrafluoroborate, which enabled subsequent displacement of 1,2-dimethylimidazole by a dibenzylamine (e.g. bis-2,4-dimethoxybenzylamine). The resulting N-diprotected, ring-substituted phenol O-sulfamates were further manipulated through reactions at the aryl substituent and finally deprotected with trifluoroacetic acid to afford a phenol O-sulfamate. The use of 2,4-dimethoxybenzyl was particularly attractive because deprotection occurred quantitatively within 2 h at room temperature with 10% trifluoroacetic acid in dichloromethane. The four key steps in the protocol described [reaction of 1,1'-sulfonylbis(2-methyl-1H-imidazole) with a phenol, methylation, displacement with a dibenzylamine and deprotection] all proceeded in very high yields.

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Elimination Mechanisms in the Aminolysis of Sulfamate Esters of the Type NH₂SO₂OC₆H₄X – Models of Enzyme Inhibitors

Cited by 16 publications

References 19 publications

Linear correlation between effective charge and bond length sensitivity to electronic effects in phosphoryl, sulfonyl, and sulfuryl compounds

Linear correlation between effective charge and bond length sensitivity to electronic effects in phosphoryl, sulfonyl, and sulfuryl compounds

Mechanisms of hydrolysis of phenyl- and benzyl 4-nitrophenyl-sulfamate esters

Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups

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